Disulfonated tetraphenyl chlorin (TPCS2a)-induced photochemical internalisation of bleomycin in patients with solid malignancies: a phase 1, dose-escalation, first-in-man trial.

BACKGROUND: Photochemical internalisation, a novel minimally invasive treatment, has shown promising preclinical results in enhancing and site-directing the effect of anticancer drugs by illumination, which initiates localised chemotherapy release. We assessed the safety and tolerability of a newly developed photosensitiser, disulfonated tetraphenyl chlorin (TPCS2a), in mediating photochemical internalisation of bleomycin in patients with advanced and recurrent solid malignancies. METHODS: In this phase 1, dose-escalation, first-in-man trial, we recruited patients (aged ≥18 to <85 years) with local recurrent, advanced, or metastatic cutaneous or subcutaneous malignancies who were clinically assessed as eligible for bleomycin chemotherapy from a single centre in the UK. Patients were given TPCS2a on day 0 by slow intravenous injection, followed by a fixed dose of 15 000 IU/m(2) bleomycin by intravenous infusion on day 4. After 3 h, the surface of the target tumour was illuminated with 652 nm laser light (fixed at 60 J/cm(2)). The TPCS2a starting dose was 0·25 mg/kg and was then escalated in successive dose cohorts of three patients (0·5, 1·0, and 1·5 mg/kg). The primary endpoints were safety and tolerability of TPCS2a; other co-primary endpoints were dose-limiting toxicity and maximum tolerated dose. The primary analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00993512, and has been completed. FINDINGS: Between Oct 3, 2009, and Jan 14, 2014, we recruited 22 patients into the trial. 12 patients completed the 3-month follow-up period. Adverse events related to photochemical internalisation were either local, resulting from the local inflammatory process, or systemic, mostly as a result of the skin-photosensitising effect of TPCS2a. The most common grade 3 or worse adverse events were unexpected higher transient pain response (grade 3) localised to the treatment site recorded in nine patients, and respiratory failure (grade 4) noted in two patients. One dose-limiting toxicity was reported in the 1·0 mg/kg cohort (skin photosensitivity [grade 2]). Dose-limiting toxicities were reported in two of three patients at a TPCS2a dose of 1·5 mg/kg (skin photosensitivity [grade 3] and wound infection [grade 3]); thus, the maximum tolerated dose of TPCS2a was 1·0 mg/kg. Administration of TPCS2a was found to be safe and tolerable by all patients. No deaths related to photochemical internalisation treatment occurred. INTERPRETATION: TPCS2a-mediated photochemical internalisation of bleomycin is safe and tolerable. We identified TPCS2a 0·25 mg/kg as the recommended treatment dose for future trials. FUNDING: PCI Biotech.

An assessment of 2 objective measurements of web space position.

PURPOSE: To describe 2 simple objective clinical methods of measuring the web position between fingers and to determine their intra-observer and inter-observer reliabilities. METHODS: Two observers examined the second, third, and fourth web spaces on both hands of 30 adult healthy volunteers. The web index measured the web height as a relative ratio to constant anatomical landmarks on both fingers subtending the web. The dorsal web index took reference from the distance between the metacarpophalangeal and proximal interphalangeal joints, whereas the palmar web index was measured in relation to the distance between the most proximal basal digital and proximal interphalangeal joint creases. The intraclass correlation coefficient was used to determine intra-observer and inter-observer reliability. RESULTS: Intraclass correlation coefficient values for intra-observer and inter-observer reliability were greater than 0.80, indicating excellent agreement. There was no statistically significant difference between the dorsal or palmar measurement methods in terms of reliability. CONCLUSIONS: The dorsal or palmar measurement method may be reliably used in healthy adults to establish a web index that describes the web position. The palmar method is considered easier to perform. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic III.

Strategies of airway management for head and neck photo-dynamic therapy.

INTRODUCTION: Photodynamic therapy (PDT) is a minimally invasive treatment modality which has great clinical implications, especially in head and neck oncology. Post-operative swelling is a well-documented consequence of PDT. It is paramount the airway remains patent for these patients. A tracheostomy remains the gold standard treatment modality for base of tongue tumours susceptible to post operative PDT inflammation, which can lead to a compromised airway. We have carried out a retrospective study to outline the airway management strategies employed for head and neck cancer patients treated with PDT and suggest recommendations for future management. MATERIALS AND METHODS: This retrospective clinical study utilises 88 patients (53 males and 35 females) treated at the UCLH Head and Neck Center, London (between 2006 and 2013), for treatment of various lesions with superficial and/or interstitial PDT, when the airway could potentially be compromised. RESULTS: Of the 88 patients selected 60 had interstitial PDT (iPDT) and 13 had superficial PDT (sPDT). Fifteen patients were treated with both iPDT and sPDT. Among the iPDT patients 19 had a trachestomy; two patients a Quicktrach; four a Cook Airway Exchange Catheter (CEAC); one a percutaneous tracheostomy; one a needle tracheostomy and 33 patients did not receive any temporary airway pathways. Among the sPDT patients two had a trachestomy. Although the majority of patients did not suffer any major incidents, one sPDT patient required an emergency tracheostomy two days post-operatively. CONCLUSION: Airway management is vital when planning PDT treatment for tongue based tumours. Consider a more conventional approach when the lesion being targeted is located at a higher risk site: Floor of mouth/posterior tongue/tongue base or when multiple oral sites are being treated.

Adrenalectomy for solitary recurrent hepatocellular carcinoma five years after living donor liver transplantation: A case report.

INTRODUCTION: The adrenal gland is a rare site for hepatocellular carcinoma (HCC) recurrence after living-donor liver transplantation (LDLT). Solitary adrenal recurrence can be managed by surgical excision, with expected better survival outcomes. We describe a rare case of successful left adrenalectomy of solitary recurrent HCC in the left adrenal gland 5 years after LDLT. PRESENTATION: 59 years male patient with HCC complicating chronic HCV infection received a right hemi-liver graft from his son. The actual graft weight was 1208 g and GRWR was 1.5. The patient started oral direct acting antiviral drugs for recurrent HCV 2 years after LDLT. A left adrenal mass was detected on follow up radiology. No other metastatic lesions were detected on metastatic workup. Left adrenalectomy was done by an anterior approach. The postoperative course was uneventful and was discharged a week after operation. Postoperative pathological and immune-histochemical examinations confirmed the metastatic HCC nature of the mass. The patient is under regular follow up with no recurrences 6 month after resection. DISCUSSION: There is no consensus regarding the management of HCC recurrence after LDLT. Most patients had multi-organ recurrences and usually offered palliative or supportive care. Solitary HCC recurrence offers a better chance for more aggressive therapy, offering better prognosis. CONCLUSION: Solitary adrenal recurrence of HCC after LDLT is extremely rare. Strict follow up protocol is necessary to allow early detection of tumor recurrence. Curative surgical resection is a safe option associated with low morbidity and expected to have a good long-term survival.